Bio L11: The Cell Cycle

What are the 4 main phases of the cell cycle?

G1, S, G2, M

What are the two groups of cell cycle phases?

• Interphase (G1, S, G2)

• M Phase (mitosis and cytokinesis)

G1 phase

Growth, preparing for S phase

S phase

DNA Replication

G2 phase

Growth and preparing for M phase

M phase → mitosis

Nuclear division

M phase → cytokinesis

Cytoplasmic division

How long does the cell cycle take in mammals?

20 hours

Post-mitotic cells

Once they exit the cell cycle, they never divide again

G0 phase

Phase that some cells enter when they temporarily stop dividing until a signal prompts them to enter G1 and restart the cycle

What two mechanisms control the cell cycle?

• Cdk

• Checkpoints

Cdk

Cyclin-dependent kinase, require cyclin proteins for activity

How does the concentration of cyclin vary throughout the cell cycle?

Cyclin is highest during mitosis and lower during interphase

What are the two different types of cyclin in cell cycle?

S-cyclin and M-cyclin

Checkpoint

Molecular mechanism that pauses the cell cycle to ensure one step is completed before the next step begins

Activated checkpoint

Cycle reaches the checkpoint and pauses at that phase

Satisfied checkpoint

Checkpoint criteria has been met and the cycle continues to the next step

G1/S Checkpoint

• Uses Cdk inhibitor proteins

• Determines whether or not cell enters cell cycle

• Checks to see if the environment is favorable or if there is DNA damage

p27

• Inhibitory proteins that bind to S-Cdk complexes during the G1/S checkpoint

• Levels of p27 must be reduced to satisfy the G1/S checkpoint

p53

• Inhibitory protein

• If DNA isn’t damaged, p53 is degraded

• If DNA is damaged, p53 binds to p21 gene and transcribes p21, a Cdk inhibitor protein

What happens if p53 loses function?

Mutations build up more rapidly because cells with DNA damage are able to pass through the G1/S checkpoint and replicate

G2/M checkpoint

• Checks to see if DNA has been completely/accurately replicated and isn’t damaged

• Enforced by Wee1 kinase

• Satisfied by Cdc25 phosphatase activity (satisfied when Cdk is activated)

Spindle assembly checkpoint

• checks that all chromosomes are attached to mitotic spindle and aligned in the center of the cell

• Ubiquitin Proteasome System (UPS)

Ubiquitin Proteasome System (UPS)

Proteasome binds to ubiquitinated proteins, unfolds bound proteins, and transfers unfolded peptide chain into proteolytic chamber

M-cyclin degradation

Triggers inactivation of M-Cdk at spindle assembly checkpoint when cyclin is destroyed in proteasome

Poly-ubiquitylation

Common signal in cells that marks a protein for destruction by the proteasome